1. health and fitness
2. disease
3. cancer

THE EVALUATION OF A REAL-TIME OPTOELECTRONIC METHOD FOR THE
DETECTION OF CERVICAL INTRAEPITHELIAL NEOPLASIA (‘CIN’)
Pruski D.1,2, Kędzia W.1,2, Przybylski M.1,2, Kędzia H.3, Józefiak A.2, Spaczyński M.1
1
Gynaecological Oncology Division, Department of Gynaecology, Obstetrics & Gynaecological Oncology, Poznan
University of Medical Sciences, Poland.
2
3
Uterine Cervix Pathophysiology Laboratory and Pathomorphology Department, Gynaecology & Obstetrics
Clinical Hospital, Poznan, Poland.
Key words: real-time optoelectronic method, cervical screening, cervical intraepithelial neoplasia, CIN.
Objectives: Biotechnology is becoming an
important tool in the prevention of cervical
cancer. One of the most promising primary
screening technologies for cervical cancer is
TruScreen, an optoelectronic medical device that
provides an immediate result. This study was
conducted to determine the effectiveness of
TruScreen in the detection of CIN.
Methods: A study was conducted on 234
women with normal or abnormal cytology results
during the period August 2006 to August 2008 by
the Laboratory of Pathophysiology of Uterine
Cervix in Gynaecology & Obstetrics Clinical
Hospital of Poznan University of Medical
Sciences. In the blinded study, a real-time
optoelectronic device (‘TruScreen’) was used for
primary cervical cancer screening followed by
HPV DNA test (Amplicor-Roche PCR), colposcopy
examination and histopathological biopsy. The
histopathological material was evaluated by two
independents pathomorphologists. Results: The
specificity for TruScreen was 82%. The sensitivity
was 63% for CIN 1 and 85% for severe grades (CIN
2/3, carcinoma planoepitheliale). The optoelectronic method did not detect the two cases of
adenocarcinoma.
Conclusions: The advantage of the optoelectronic device over cytology and colposcopy is
its ability to generate an immediate and objective
result automatically at the end of the
examination and its ease of use. TruScreen is an
effective tool for the detection of cervical
neoplastic changes and is potentially an
important improvement to the traditional
cervical screening process.
Introduction
Cervical cancer is a significant health issue for
women worldwide. In many developing countries
it is the most common malignancy amongst
women [1]. Over 3000 Polish women were
diagnosed with cervical cancer in 2005 accounting
for 5% of all oncologic diagnoses in the female
population. The morbidity and mortality rates for
cervical cancer in Poland are estimated to be
11.5% and 5.7% respectively [2].
The etiology of this cancer follows HPV infection,
particularly high oncogenic types such as HPV 16
and 18 [3]. Type 16 is related to the pathogenesis
of squamous cervical cancer, whilst type 18 is
associated with glandular cervical cancer.
The pre-cancerous stage of cervical cancer is
typically referred to as cervical intraepithelial
neoplasia (‘CIN’). There are three grades of
neoplasia: mild, moderate and severe (CIN 1, CIN
2, and CIN 3 respectively).
Cervical cancer
neoplasia of severe grade CIN 3 includes preinvasive cervical cancer, carcinoma-in-situ (‘CIS’).
It may take 3-10 years before CIN develops into
cervical cancer. Mild grade CIN is often the result
of a temporary HPV infection and 80% of these
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tissue change events do not require treatment as
they naturally clear themselves within a few
months. However, persistent HPV infection,
caused by oncogenic viral types are associated
with unfavourable prognoses and may develop
into CIN 2 /3 and then into cervical cancer.
In 1942, the first classification system of
cytological smear evaluation was suggested by
Papanicolaou [4]. The implementation of these
‘pap tests’ reduced the morbidity rate of cervical
cancer by 50% and mortality by 70% [5]. In 1988, a
new system of cytological smear evaluation was
introduced – The Bethesda System (‘TBS’). Its
improved categorisation of neoplasia states
resulted in reduced false negative and false
positive results. However, despite introducing TBS,
sensitivity and specificity of the Pap test, used to
diagnose cervical intraepithelial neoplasia, has still
not exceeded 70% and 80% respectively. The
introduction of molecular methods to identify
oncogenic HPV types has simplified the
qualification of women into the cervical
intraepithelial neoplasia high risk group. The only
diagnostic method and ‘gold standard’ is
histopathology where the specimen is obtained
from the suspected lesion during colposcopy.
The ever increasing financial constraints on the
health systems in most countries drives the
demand for cheaper and more efficient cervical
screening & treatment programs. The World
Health Organisation has defined a need for
“prevention programs that are viable in lowresource settings and achieve high screening
coverage, offer effective and acceptable test &
ensure appropriate treatment of test-positive
women”. This suggests that the ideal solution for
many countries is a non-invasive, screening tool
that provides an accurate & objective result, which
is available immediately and does not require
laboratory work and follow-up. It should allow the
clinician to diagnose pathology as well as define
the diagnostic process within one controlled visit.
Biophysics is becoming an important field in the
area of cervical cancer prevention and diagnosis.
These technologies can have an advantage over
cytology in terms of a lower percentage of false
positive and negative results. One of the most
promising technologies for use in cervical cancer
prevention programs is TruScreen.
TruScreen is a primary cervical screening tool for
the detection of pre-cancerous and cancerous
tissue. TruScreen is a novel opto-electronic device,
which uses low-level electrical and optical signals
to scan the cervix [6]. The response is measured,
and computer-based expert system software is
then used to classify the tissue response, by
comparing the signals with those stored in a
computer database representative of the range of
cervical tissue types [7].
If the tissue is abnormal, the TruScreen technology
will allow the clinician to immediately make
management decisions and communicate these
decisions to the patient. Therefore it may
minimise the labour intensive follow-up and lessen
the chance of a patient being lost to recall.
TruScreen comprises a hand piece connected to a
compact processing and interpretation console
with disposable single use only sheath. The tip of
the probe, which is in contact with the cervix,
scans the tissue by repetitively pulsing it with low
levels of optical and electrical energy. Real-time
interpretation of the cervix tissue response is
achieved by automatic comparison with a digitally
stored catalogue of tissue signatures [8].
The hand piece of is a long, thin, pen-shaped
instrument approximately 310 mm in length,
which is hand-held by the operator. The section of
the probe that enters the vagina is less than 150
mm in length with a tip diameter less than 7mm.
The tip is used by the operator to scan the cervix
during the TruScreen examination.
The TruScreen delivers multiple electrical pulses of
0.8V for a duration of 100 microseconds. The
resulting electrical decay curves are measured and
salient features used as an input for the expert
system.
The optical measurements operate within the
visible and near infrared spectrum. The light
emitting diodes (LEDs) have a power output range
of 7-130 microwatts. The light intensity is far
below that of the colposcope. Four LEDs are used
2
to emit light at three discrete wavelengths. The
reflected and backscattered light is measured and
this tissue response forms an additional input for
the expert system. The electrical and optical
measurement cycles is completed 14 times per
second.
A disposable sheath or Single Use Sensor (‘SUS’)
covers the hand piece, and this sheath is discarded
after use. This hand piece is part of the TruScreen
device.
TruScreen was granted regulatory approval (CE
Marking) by the European regulatory authorities in
2002, as a screening instrument for the detection
of cervical pre-cancer and cancer.
A confirmation of the value of TruScreen in
detecting CIN could have a significant impact on
the current cervical cancer rate in Poland by
facilitating the wider implementation of
prevention programs as well as the earlier
detection of cervical intraepithelial neoplasia.
Objective
To evaluate the sensitivity and specificity of
TruScreen, a non-invasive device that uses optoelectronic technology to detect cervical
intraepithelial neoplasia.
Methods & Materials
A study was conducted on 234 women with
normal or abnormal cytology results during the
period August 2006 to August 2008 by the
Laboratory of Pathophysiology of Uterine Cervix in
the Gynaecology & Obstetrics Clinical Hospital of
Poznan University of Medical Sciences. A real-time
opto-electronic device (‘TruScreen’) was used to
screen for cervical cancer with the results
encrypted until the final histopathological
diagnosis. The study was approved by the
Bioethics Committee of the University and each
patient provided a written consent. The patients
underwent
the
following
examinations:
TruScreen, repeat of cytological examination, HPV
DNA test, colposcopy and biopsy/histology.
TruScreen examination
The examination was performed with the use of
TruScreen.
The device was developed and
manufactured by Polartechnics Ltd. Obtaining the
result is straightforward, takes only 1-2 minutes
and is painless for the patient. A new disposable
cover is placed over the biosensor probe and then
its tip is moved around the cervix in a pre-defined
pattern with guidance from the ‘stop-go traffic
light’ LEDs located on the hand piece. To ensure
trial validity the TruScreen device was pre-set to
‘encryption mode’ whereby the operator was
unable to see whether the result was ‘normal’ or
‘abnormal’ but the data could be extracted at a
later date.
Viral examinations
The material for the presence of oncogenic types
of human papilloma virus (DNA HPV HR) was
collected with the Cervex Brush from the
ectocervix, endocervical canal and the cervical
fornicibus. It was then processed using PCR
method (Amplicor – Roche).
Colposcopic examination
The examination was performed with the use of a
stereoscopic colposcope (Olympus OCS – 500).
Each examination was performed with 3-5% acetic
acid and Schiller test. For the colposcopic view
evaluation, the eight points Reid’s scale was used
to evaluate the border, whiteness, iodo-negative
and vessels of changes. Three points or greater
indicated an incorrect result.
Biopsy of suspected lesions
A biopsy was taken from suspected lesions of the
cervix with endocervical abrasion. In the case of an
unsatisfactory colposcopy, four biopsies and
abrasions were performed.
If the results from colposcopy, cytology and
TruScreen were all negative then the
histopathological examination was not performed.
If any of the results were positive then a full
histopathological examination was performed,
which included biopsy and endocervical curettage.
All histopathological examinations were blinded
and evaluated by two independent pathologists.
Results
The percentage of abnormal histopathology results
in the examined group 63/234 was 27%.
The examined group was divided according to
histopathologic results into the following groups as
shown below and in Figure 1:
- 27 patients with CIN 1 diagnosis
- 15 patients with CIN 2 diagnosis
3
- 12 patients with CIN 3 diagnosis
- 6 patients with carcinoma planoepitheliale – CA
diagnosis
Table 1. Sensitivity of opto-electronic method when
compared against histopathologic diagnoses CIN 1,
CIN 2, CIN 3, carcinoma planoepitheliale(‘CA’) and
adenocarcinoma (‘ACA’).
BIOPSY RESULT
TRUSCREEN TRUE
POSITIVE
TRUSCREEN FALSE
NEGATIVE
SENSITIVITY
- 3 patients with adenocarcinoma – ACA diagnosis
CIN1
27
17
10
63%
In the case of CIN 2 changes, the sensitivity was
higher at 80%. In the population of 15 women
with confirmed pathology, we obtained three false
negative results as shown in Table 1.
CIN2
15
12
3
80%
CIN3
12
10
2
83%
For CIN 3 changes the sensitivity of the optoelectronic method was higher again at 83%. The
sensitivity increased to 100% for cases of
carcinoma planoepitheliale. The method did not
detect the two cases of adenocarcinoma change
(Table 1).
CA
6
6
0
100%
ACA
3
0
3
0%
- 171 patients with diagnosis lacking neoplasia
features.
TRUSCREEN
FALSE
NEGATIVE
SENSITIVITY
Table 2. Sensitivity for intraepithelial changes of
low grade in the area of squamous epithelium (CIN
1) and for high grade (CIN 2, CIN3, Carcinoma
planoepitheliale).
TRUSCREEN
TRUE POSITIVE
Specificity for normal results came to 82%.
Sensitivity for intraepithelial changes of low grade
(CIN 1) in the area of squamous epithelium was
63%, and for high grade (CIN 2, CIN3, Carcinoma
planoepitheliale) it increased to 85% (Table 2).
BIOPSY RESULT
The sensitivity of the opto-electronic method in
the case of histopathologic diagnosis for cervical
intraepithelial neoplasia of low grade (CIN 1) was
63%. The method allowed us to identify 17
pathological cases out of the group of 27 women
as shown by the final diagnosis in Table 1.
LOW
GRADE
27
17
10
63%
HIGH
GRADE
33
28
5
85%
The test for the presence of oncogenic types of
human papilloma virus, DNA HPV HR, detected all
three cases of adenocarcinoma in the area of the
mucous membrane of cervix.
The specificity of colposcopy for the normal results
came to 54%. Sensitivity of colposcopy for
intraepithelial changes of low grade (CIN 1) in the
area of squamous epithelium was 85% and for high
grade (CIN 2, CIN3, Carcinoma planoepitheliale) it
increased to 97% (Table 3).
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OPTOELECTRONIC
METHOD
COLPOSCOPY
Table 3. Comparison of sensitivity and specificity of
opto-electronic method and colposcopy
HIGH GRADE
85%
97%
LOW GRADE
65%
85%
NORMAL
82%
54%
Figure 3. The percentage of normal (n=149) and
abnormal (n=85) Pap test in the examined group
Figure 1. The percentage of normal and abnormal
histopathology results in the examined group
Discussion
There is an opportunity with new cervical
screening methods to improve sensitivity and
specificity rates and identify patients with
neoplasia more effectively by using automated
processes which eliminate the risk of human error.
TruScreen offers the advantage of providing an
immediate result thereby reducing the number of
patient visits, shortening the screening-treatment
timeline and ultimately reducing the cost of
cervical cancer prevention programs.
Figure 2. The percentage of normal (n=159) and
abnormal (n=75) results of opto-electronic method
in the examined group
The results obtained by our team confirm the
advantage of TruScreen over traditional cytology.
In trials previously performed in Australia and the
United Kingdom, sensitivity in the area of
squamous epithelium was 67% (70% for high grade
lesions) whereas the sensitivity using cytology was
43% (69% for high grade lesions)[9].
In 1997 Mould and fellow workers designed a
questionnaire to evaluate patient comfort when
having Pap and TruScreen tests performed. The
questionnaire was completed by 152 patients.
Most of the examined population regarded
TruScreen as the most comfortable and painless of
the two methods. Approximately 98% of patients
claimed that the major advantage of the method
was the immediate result. None of the women
reported any pain during the examination with
TruScreen [10].
A key advantage of the TruScreen examination is
the possibility of finally eliminating the human
error during cervical screening, which historically
has often been an issue caused by the
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inexperience of the doctor or colposcopist. The
technology is objective, inexpensive, offers an
immediate result and, most importantly, does not
rely on the clinical experience of the person
performing the examination. This simplification of
the screening programme together with the
performance improvement may facilitate the
adoption of such innovative technologies to
combat cervical cancer [11].
The device is suitable for general screening,
however it is not recommended for use if the
patient has had a recent cervical procedure,
radiotherapy, has excessive bleeding or is currently
pregnant.
Similar to cytology and colposcopy the optoelectronic method is unable to identify neoplasia
located in the endocervix as demonstrated by the
two cases of adenocarcinoma. TruScreen may be
able to detect such cases where the disease is also
present on the ectocervix, however further data is
required to draw reliable conclusions.
7. S C Quek,*MRCOG, T Mould,*MRCOG, K Canfell,**BE (Hons),
A Singer,***PhD, FRCOG, V Skladnev,†BSc, ME, M
Coppleson,‡MD, The Polarprobe—Emerging Technology for
Cervical Cancer Screening FRACOG,FRCOG Cervical Screening:
September 1998, Vol. 27 No. 5.
8. Coppleson M, Canfell K, Skladnev V. The Polarprobe — An
instantaneous optoelectronic approach to cervical screening.
CME J Gynecol Oncol 2000; 5: 31—8.
9. Singer A, Coppleson M, Canfell K et al. A real time
optoelectronic device as an adjunct to the Pap smear for
cervical screening: a multicenter evaluation. International
Journal of Gynecological Cancer 2003; 13: 804–811.
10. Mould TAJ, Quek SC, Lovegrove J, Gallivan S, Singer A. The
acceptability of cytological screening for cervical cancer
compared to a new electronic screening device - the
Polarprobe, Proceedings of the EUROGIN Third International
Congress; 1997 March 24-27; Paris. Paris: European Research
Organization on Genital Infection and Neoplasia, 1997.
11. Pruski D, Kedzia W, Przybylski M, [et al.]. Assesment of real
optoelectronic method in the detection of cervical
intraepithelial neoplasia. Ginekol Pol. 2008 May; 79(5):342-346.
Conclusion
The advantage of TruScreen over cytology and
colposcopy is its ability to generate an immediate
and objective result automatically at the end of
the examination and its ease of use.
TruScreen is an effective tool for the detection of
cervical neoplastic changes and is potentially an
important improvement to the traditional cervical
screening process.
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